Listener Detection of Objectively Validated Acoustic Features of Speech in Huntington's Disease.

BACKGROUND: Subtle progressive changes in speech motor function and cognition begin prior to diagnosis of Huntington's disease (HD). OBJECTIVE: To determine the nature of listener-rated speech differences in premanifest and early-stage HD (i.e., PreHD and EarlyHD), compared to neurologically healthy controls. METHODS: We administered a speech battery to 60 adults (16 people with PreHD, 14 with EarlyHD, and 30 neurologically healthy controls), and conducted a cognitive test of processing speed/visual attention, the Symbol Digit Modalities Test (SDMT) on participants with HD. Voice recordings were rated by expert listeners and analyzed for acoustic and perceptual speech features. RESULTS: Listeners perceived subtle differences in the speech of PreHD compared to controls, including abnormal pitch level and speech rate, reduced loudness and loudness inflection, altered voice quality, hypernasality, imprecise articulation, and reduced naturalness of speech. Listeners detected abnormal speech rate in PreHD compared to healthy speakers on a reading task, which correlated with slower speech rate from acoustic analysis and a lower cognitive performance score. In early-stage HD, continuous speech was characterized by longer pauses, a higher proportion of silence, and slower rate. CONCLUSION: Differences in speech and voice acoustic features are detectable in PreHD by expert listeners and align with some acoustically-derived objective speech measures. Slower speech rate in PreHD suggests altered oral motor control and/or subtle cognitive deficits that begin prior to diagnosis. Speakers with EarlyHD exhibited more silences compared to the PreHD and control groups, raising the likelihood of a link between speech and cognition that is not yet well characterized in HD.

Cortisol and depression in pre-diagnosed and early stage Huntington's disease.

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction and depression have both been shown to occur in Huntington's disease (HD) gene carriers prior to diagnosis (pre-HD) and in diagnosed HD patients. However, the relationship between HPA axis dysfunction and the severity of depressive symptomatology in pre-HD and early-HD has not been systematically examined, despite morning hypercortisolism being a characteristic feature of some subtypes of idiopathic depression. The aim of this study was to investigate whether HPA axis function is related to levels of depression in pre-HD and early-HD. To assess HPA axis function we obtained salivary cortisol concentrations from 20 controls, 20 pre-HD, and 17 early-HD participants at four time points over a 24h period. Depression symptoms were assessed using the Inventory of Depressive Symptomatology - Self-Report. Of the participants who were found not to be depressed, the early-HD group had significantly lower morning cortisol levels relative to pre-HD and controls. In contrast, the early-HD group with at least mild or greater levels of depression symptoms had a comparable cortisol concentration to pre-HD and controls. The results suggest that early-HD may be associated with hypocortisolism. However when depressed, a hyperactive HPA axis response may still be induced in early-HD and lead to cortisol levels that are similar to pre-HD and controls. Our study reveals that cortisol levels in HD may be modified by the presence or absence of depressive symptomatology. Depression may be an important factor for understanding how the HPA axis is affected in HD, particularly in the morning.

The relationship between cortisol and verbal memory in the early stages of Huntington's disease.

Hypothalamic pituitary adrenal (HPA) axis hyperactivity has been linked to learning and memory difficulties in a range of neurodegenerative and neuropsychiatric conditions. In Huntington's disease (HD), both declines in learning and memory and HPA axis dysfunction are present early in the disease. However, the relationship between specific learning and memory deficits and HPA axis functioning in HD has not been examined. The aim of this study was to investigate cortisol levels in relation to verbal learning and memory in pre-diagnosed (pre-HD) participants and patients at the early stages of diagnosed HD (early-HD). Cortisol concentration was assayed in saliva samples from 57 participants (17 early-HD, 20 pre-HD, and 20 controls) at four time-points across a 24-h period. Verbal memory was assessed using the California Verbal Learning Test-Second Edition (CVLT-II). We focused statistical analyses on the late evening cortisol concentration, and examined cortisol levels and verbal memory function in relation to diagnostic group (control, pre-HD, early-HD), and in a separate set of analyses combining pre-HD and early-HD (and excluding controls) we also examined cortisol and verbal memory performance in relation to the severity of HD-related motor signs. Of these two classification approaches, HD motor sign severity was more strongly associated with high evening cortisol levels and both reduced information encoding and memory retrieval. Separately, there was also a trend of higher cortisol levels in pre-HD. The findings suggest hypercortisolism and the underlying pathological changes may begin many years before a clinical diagnosis is made, but the memory decline associated with HPA axis disturbance may only become detectable once motor signs become pronounced.

The experience of seizures after epilepsy surgery.

Postoperative seizures occur in 20-60% of patients who have epilepsy surgery. Despite this, there is limited understanding of a patient's experience of the recurrence of seizures after surgery. This study used a qualitative approach to identify key themes derived from content analysis of 15 in-depth patient interviews about the experience of seizure recurrence. The results showed a prominence of psychological issues over medical concerns. The four most frequently expressed themes were perceived success of surgery, medication, acceptance of seizure recurrence, and personal independence. Despite seizure recurrence, patient sentiments were not universally negative; rather there was heterogeneity of views, with some reporting ambivalence and others a sense of satisfaction with outcome. The findings provide evidence for the importance of cognitive reframing and benefit finding in the context of seizure recurrence.